Dr. Jonathan Wigginton, MD, National Cancer Institute. Dr. Wigginton is Head of the Investigational Biologics Group at NCI and was recently appointed Head of the NCI-CCR Translational Research Initiative. He earned his medical degree from the U. of Mich. Ann Arbor and completed fellowship training in Pediatric Hematology-Oncology at the NCI.
There are two types of immune systems, the innate immune system and the adaptive immune system, which work in concert with each other. The role of cytokines is to regulate the response between them.
Studies have been conducted in animal models (animals that have responses similar to people) and have identified IL-18 as an Interferon Gamma inducing factor. (The Interferon most KIDNEY-ONC list members are familiar with as a treatment is Interferon Alpha.) In combination with IL-2, IL-18 greatly enhances Interferon Gamma production.
In murine (mouse) lung cancer studies, IL-18 treatment elicited an 80% response rate. Reintroducing tumors into mice with a previous complete response to lung cancer produced rejection of the tumors, so the adaptive immune system had learned a response.
In murine metastatic RCC a 60% response rate has been observed with IL-18 treatment. IL-12 with pulsed IL-2 produced a similar response.
This will be moving to Phase 1 trial.
[Editor's Note: This means that IL-18 hasn't ever been tested in a human being. It won't be available until the Phase I trial starts, and then only in clinical trials. (Phase I trials are dose finding studies.) It's important to remember that many things which are extremely promising in the lab don't work out in the clinic, so while remaining hopeful that this will be the next big breakthrough in the treatment of metastatic renal cell carcinoma, it's important to keep these exciting preclinical results in proper perspective.]